Imaging Technique Explored As Depression Treatment

For years, electroconvulsive therapy (ECT) was the only treatment that used an electrical stimulus to counter depression. As the 2lst century unfolds, however, some other depression therapies using electrical or magnetic stimulation are becoming available as well.

Specifically, vagus nerve stimulation was approved by the U.S. Food and Drug Administration in February for use in treatment-resistant depression. Repetitive transcranial magnetic stimulation (rTMS) shows encouraging clinical results (Psychiatric News, May 7, 2004) as does magnetic seizure therapy (Psychiatric News, June 4, 2004). And now it looks as though low-level magnetic field stimulation might help as well.

Benefits Found by Happenstance

A new MRI brain-scanning technique called echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) emits low-level magnetic fields. It is designed to measure the concentration of certain chemicals in the brain, providing a rough map of their location. Several years ago, some bipolar disorder subjects happened to mention that they felt less depressed after being exposed to this technique.

This fortuitous discovery prompted Michael Rohan, an imaging physicist at Harvard-affiliated McLean Hospital in Belmont, Mass., and colleagues to wonder whether the low-level magnetic fields emitted during EP-MRSI scanning might be able to exert antidepressive effects.

The researchers exposed 30 subjects with bipolar disorder and 14 healthy comparison subjects to low-level magnetic fields emitted during EP-MRSI scanning; 10 bipolar-disorder subjects received a sham treatment. All three groups were assessed for mood changes immediately before and immediately after treatment using the Brief Affect Scale, a structured mood-rating scale.

Twenty-three of the 30 bipolar subjects exposed to the low-level magnetic fields experienced an improvement in mood after treatment—a significant difference. Such a significant difference was absent in the bipolar-disorder subjects given a sham treatment (only three experienced mood improvement after treatment), and a significant difference was also absent in the healthy comparison subjects among whom only 4 out of 14 experienced improvement after treatment.

“These preliminary data,” Rohan and his co-workers reported in the January 2004 American Journal of Psychiatry “suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. Overall response rates to the EP-MRSI scan were consistent with rates reported in current rTMS depression treatment trials.”

Results Prompt Animal Study

These encouraging findings prompted William Carlezon, Jr., Ph.D., director of McLean Hospital's Behavioral Genetics Laboratory, along with Rohan and other co-workers, to see whether they could demonstrate in rodents what they thought they were seeing in humans.

Thirty-two rats were given a forced swim test. This is an animal model often used in the study of depression. It is a two-day learned helplessness procedure in which rats swim under conditions in which escape is not possible.

All of the rats were then placed in a device to stimulate the skull with low-level magnetic fields. One-fourth were then exposed to low-level magnetic fields administered within the focal point of the field, one-fourth to low-level magnetic fields administered outside the optimal focal point of the field, one-fourth to a constant direct-current magnetic field gradient within the focal point of the field, and one-fourth received no magnetic field exposure.

All of the animals were again given a forced swim test, and their posttreatment behaviors compared with their pretreatment ones.

The group that had been exposed to low-energy magnetic fields administered within the focal point of the field demonstrated decreased immobility and increased swimming, compared with their performance during the first forced swim test. This was not the case for the group that had been exposed to low-level magnetic fields administered outside the focal point of the field or for the group that had been exposed to a constant direct-current magnetic field or the group that had simply been placed in the device. Moreover, the decreased immobility and increased swimming seen in the first group were similar to those usually seen in rats put through a forced swim test and then given SSRI antidepressants.

Putting these results together, it appears that “relatively weak magnetic stimulation can have antidepressant-like effects in rodents, consistent with recent reports in humans treated during the depressive phase of bipolar disorder,” Carlezon and his team concluded in the March 15 Biological Psychiatry.

“This is good solid work,” Mark George, M.D., said in an interview with Psychiatric News. George is a professor of psychiatry, radiology, and neurology and director of the Brain Stimulation Laboratory at the Medical University of South Carolina. “[However], it is important that some group other than the McLean group tests these results in humans and animals. External replication is the hallmark of science.”

He added that “it is not at all clear how these antidepressant effects are happening. My first guess would be that they are not the same as what we are producing with TMS. In TMS.. .antidepressant effects.. .occur at intensities strong enough to depolarize cortical neurons.... I would bet that these effects are either caused by changes in protein morphology and receptor binding or are due to induced electrical currents in limbic regions.”

“We are trying to identify what the low-field magnetic stimulation does to the brain that might cause these effects,” Carlezon told Psychiatric News. “Currently, we are doing two things. First, we are seeing if low-field magnetic stimulation alters the way certain brain cells fire. The limitation here is that you need to know which brain regions to look at. We plan to look at brain regions containing large numbers of serotonin neurons, since the effects of low-field magnetic stimulation resembled those of fluoxetine. Second, we are seeing if low-field magnetic stimulation affects gene expression in the brain.... The limitation here is similar—which brain regions should we study? The techniques we use allow us to study them all, although this type of work takes a long time.”

During the next few years, George anticipates, progress will be made in understanding how these various electromagnetic tools counter depression. It is also likely, he predicted, that modulating the brain with electromagnetic fields will “produce therapeutic effects more pronounced than those from current medications.. .because of the ability to target specific regions and more than one region at once.”

Nonetheless, he does not foresee that such neuromodulation will replace oral medications and talk therapies, but rather will complement them.

The pilot clinical trial conducted by Rohan and colleagues was financed by the National Institute of Mental Health, the Poitras Foundation, the Stanley Foundation Bipolar Disorders Research Center at McLean Hospital, and John and Virginia Taplin. The rodent studies conducted by Carlezon and co-workers were financed by the National Institute of Mental Health, a Johnson and Johnson Focused Giving Award, the Stanley Medical Research Institute, and the Poitras Foundation.

The study, “Low-Field Magnetic Stimulation in Bipolar Depression Using an MRI-Based Stimulator,” is posted online at<http://ajp.psychiatryonline.org/cgi/content/full/161/1/93>?. An abstract of “Antidepressant-like Effects of Cranial Stimulation Within a Low-Energy Magnetic Field in Rats” is posted online at<http://journals.elsevierhealth.com/periodicals/bps>.▪

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